Tissue monitoring system for intravascular infusion

ABSTRACT

An infusion system has a capability to monitor infusion complications such as extravasation, tissue necrosis, infiltration, phlebitis, and blood clots. The infusion system has at least partially transparent flexible film barrier dressing in a flexible membrane that incorporates a plurality of sensors capable of detecting tissue condition and a control unit capable of coupling to the film barrier dressing that monitors signals from the sensors. A device is capable of executing non-invasive physiological measurements to characterize physiologic information from cross-sectional surface and subcutaneous tissue to detect the presence or absence of tissue conditions such as infiltration or extravasation during intravascular infusion. In some examples, the device utilizes depth-selective methods to sense, detect, quantify, monitor, and generate an alert notification of tissue parameters.

RELATED PATENTS AND APPLICATIONS

This application is related to U.S. patent application Ser. No.60/351,094, filed on Jan. 25, 2002.

The disclosed system and operating method are related to subject matterdisclosed in the following co-pending patent applications that areincorporated by reference herein in their entirety:

1. U.S. patent application Ser. No. 10/226,648 entitled, “Film BafflerDressing for Intravascular Infusion Tissue Monitoring System”, namingKaren Jersey-Willuhn and Manuchehr Soleimani as inventors and filed oneven date herewith;

2. U.S. patent application Ser. No. 10/227,175, entitled “ConductivityReconstruction Based on Inverse Finite Element Measurements in a TissueMonitoring System”, naming Karen Jersey-Willuhn and Manuchehr Soleimanias inventors and filed on even date herewith.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates generally to physiological monitoring devices and,more particularly, to tissue monitoring devices and methods fordetecting harmful conditions including conditions that occur duringintravascular infusion.

2. Relevant Background

An infusion system is commonly used to infuse a fluid into a patient'svascular system. Intravenous (IV) therapy is sometimes necessary forpatient treatment and is generally considered a safe procedure. IVtherapy is administered to approximately 80% of hospitalized patients inthe United States. Some form of IV complication develops in nearly athird of patients receiving IV therapy. Most complications do notprogress to more serious problems, but cases with further complicationsof IV failure are difficult to predict.

Several complications may arise from the infusion process includingextravasation, tissue necrosis, infiltration, phlebitis, venousinflammation, and others. These complications can result in prolongedhospitalization, infections, patient discomfort, patient disfigurement,nerve damage, and additional medical complications and expense.Phlebitis is the largest cause of intravascular infusion morbidity.Infiltration and extravasation follow only phlebitis as IV morbiditycauses.

When complications of infiltration, extravasation, phlebitis, or bloodclots occur, the standard of care requires prompt removal of the IV tominimize further complications since continued pumping of infusateexacerbates the complications. Immediate detection of complications andtermination of infusion reduces the possibility and damage of furthercomplications. IV complications can cause failure to infuse a neededdrug or fluid and lead to inadequate or sub-optimal therapeutic druglevels and hypo-volemia. Fluids that would lead to patient recovery mayfail to reach the appropriate organs or tissue. Under life-threateningconditions or where infusion is life-sustaining, a patient's failure toreceive fluids can be lethal. IV failure compromises patient safety.

Infiltration is the inadvertent administration of solution intosurrounding tissue. Extravasation is the inadvertent administration of asolution that is capable of causing tissue necrosis when the materialescapes or is infused outside the desired vascular pathway.

Extravasation sometimes results when an injection fluid, for example acontrast medium, is injected into a blood vessel. Extravasation is theaccidental infusion of injection fluid into tissue surrounding a bloodvessel rather than into the intended blood vessel. Various causes ofcomplications that may occur with intravenous infusions include fragilevasculature, valve disease, inappropriate needle placement, infusionneedle dislodgement of the cannula or needle delivering the fluid,microdilation of veins due to infusate chemical properties causing thematerial to leak from the vein. dislodgement from the vessel due topatient movement, or infusion needle piercing through the vessel wallalso due to patient movement. IV complication risk increases for elderlypersons, children, cancer patients, and immuno-compromised patients.

Patients under therapy with vesicant drugs including chemotherapy,infusion of highly osmotic solutions, or high acid or low base solutionshave risk of tissue necrosis if fluids are infused outside the vascularpathway. Examples infused agents include total parenteral nutrients,chemotherapeutic alkalating drugs, alkaline solutions, vasopressors (forexample, Total Parenteral Nutrition (TPN)), antibiotics, hypertonicacids, KCl, and others. Many routinely-used antibiotics and medicationsare capable of causing extravasations and tissue necrosis.Antineoplastics can cause severe and widespread tissue necrosis ifextravasation occurs. Chemotherapeutic agents are highly toxic IV drugs.Several drugs for emergency use have a well-documented high incidence oftissue damage. For example, administration of essential vasopressor drugdopamine in life-threatening or life-sustaining situations has adocumented incidence of 68% tissue necrosis or extravasation at the IVinfusion site. Caretakers cannot anticipate which complication willprogress including necrosis to muscle.

Complications that may occur can cause serious patient injury by tissuetrauma and toxicity of injection fluid. For example some injectionfluids such as contrast media or chemotherapy drugs can be toxic totissue if undiluted by blood flow. As a consequence, extravasationshould be detected as early as possible and injection immediatelydiscontinued upon detection.

In infiltration and extravasation, a condition occurs in which infusedfluid enters extravascular tissue rather than the blood streamoccurring, for example, when an infusion needle is not fully inserted tothe interior of a blood vessel. Infiltrating fluid is infused intointerstitial spaces between tissue layers, preventing proper intravenousdrug administration and possibly resulting in toxic or caustic effectsof direct contact of infused fluids with body tissues.

Infiltration and extravasation complications are costly and compromisepatient outcome. Complications include pain and prolonged discomfortthat may last for months, prolonged healing, ischemic necrosis due tovasoconstriction, opportunistic infections and septicemia, ulceration,cosmetic and physical disfigurement, and direct cellular toxicity forantineoplastic agents. Other complications include skin grafting, flaps,and surgical debridements, sometimes multiple. Further complications arecompartment syndrome, arteriolar compression, vascular spasm, nervedamage (sometimes permanent), muscular necrosis, functional muscularchanges, functional loss of extremities, amputation, reflex sympatheticdystrophy, and chronic pain syndrome.

Infiltration and extravasation can cause catheter-related bloodstreaminfection, including sepsis. An estimated 200,000 to 400,000 incidencesof catheter-related infections occur annually, resulting inapproximately 62,500 deaths, 3.5 million additional hospital days fortreatment, and adds about $3.5 billion to the annual healthcare cost.Estimates of individual costs vary. A catheter-related bloodstreaminfection may cost $6,000 to $10,000 per incidence, and increase thehospital stay by up to 22 days.

Additional costs can be incurred. Additional medications may need to beinjected to dilute or neutralize the effect of toxic drugs once tissuenecrosis has begun to decrease the caustic reaction and reduce tissuedamage. Surgical removal of the necrotic tissue may be required.Caretaker time, and therefore costs, increase since the extremitiestypically need to be elevated to improve venous return, warm and coolpacks are applied, psychological comfort and pain medications given, andseverity of the complication is monitored. A septic infection may causea serious infection such as an infection in the heart.

Other conditions that result from improper supply of fluid to a patientin intravenous therapy include venous inflammation and phlebitis,swelling at the infusion site. Phlebitis complications includeinflammation or thrombophlebitis that occurs with about 10% of allinfusions. If phlebitis continues as the duration of infusion continues,the duration of the complication also increases. Phlebitis predisposes apatient to local and systemic infection. Phlebitis often results in acomplication of infection resulting from use of intravenous lines.Underlying phlebitis increases the risk of infection by an estimatedtwenty times with estimated costs of IV infections between $4000 and$6000 per occurrence. When phlebitis is allowed to continue, the veinbecomes hard, tortuous, tender, and painful for the patient. The painfulcondition can persist indefinitely, incapacitates the patient, and maydestroy the vein for future use. Early assessment of complication andquick response can reduce or eliminate damage and save the vein forfuture use.

Another possible complication is blood clotting. IV needles and cannulascan become occluded with blood clots. As an occlusion intensifies,mechanical failure of the infusion can occur. Prescribed therapy cannotbe administered if the catheter is occluded and multiple othercomplications can result, such as pulmonary embolism. Complications mayprogress, forming a thrombus and causing thrombophlebitis, orcatheter-associated infections or bactermias.

Tissue necrosis may result when some of the infused materials arevesicant or other materials are infused outside the vascular pathway.

The current methods for detecting phlebitis, necrosis, infiltration orextravasation in a medical surgical patient undergoing therapeuticinfusion are visual inspection and notification of pain by the patient.A caretaker visually inspects the intravascular insertion site oraffected body parts for swelling, tenderness, discoloration. Otherwise,the caretaker requests or receives notification of pain by the patientbut generally when tissue damage has begun.

Another problem that occurs with infusion is that the patient normallydoes not eat so that vital electrolytes can be lacking, a condition thatis exacerbated by the patient's illness. One critical electrolyte ispotassium. Medical protocols exist to replace needed potassium, but thelevel of replacement is difficult to determine. Low or high levels ofpotassium can lead to cardiac irritability and other complications.Electrolyte levels are commonly determined by electrochemistry testing,usually by blood draws, a painful procedure that commonly involves timedelays for analysis.

What are needed are safe, reliable devices and methods that supplyinformation on patient status of the presence or absence of IVcomplications. What are further needed are devices and methods thatnotify a caretaker of the occurrence of infiltration, extravasation,phlebitis, blood clots, and electrolyte levels with sufficient quicknessto reduce or eliminate tissue damage, patient discomfort, and additionalcomplications and associated costs.

SUMMARY OF THE INVENTION

An infusion system has a capability to monitor infusion complicationssuch as extravasation, tissue necrosis, infiltration, phlebitis, andvenous inflammation.

An infusion system comprises an at least partially transparent flexiblefilm barrier dressing in a flexible membrane that incorporates aplurality of sensors capable of detecting tissue condition and a controlunit capable of coupling to the film barrier dressing that monitorssignals from the sensors.

A device is capable of executing non-invasive physiological measurementsto characterize physiologic information from cross-sectional surface andsubcutaneous tissue in one, two, or three dimensions to detect thepresence or absence of tissue conditions such as infiltration orextravasation during intravascular infusion. In some embodiments, thedevice utilizes depth-selective methods to sense, detect, quantify,monitor, and generate an alert notification of tissue parameters.

In some examples, the device uses one or more sensing technologiesthrough a sensor pathway. Suitable sensing technologies includebio-impedance sensing and photonics, for example, that can be combinedto obtain data points that are stored, compared to a preset threshold orpattern, quantified and displayed to a visual display screen.

Some systems can include an auditory alert signal that annunciates upondetection of infiltration and extravasation. The system can respond todetection by adjusting the infusion rate at the infusion pump to reduceadditional complications. The notification system enables medicalsurveillance of patient tissue status during infusion to allow acaretaker to intervene early to reduce injury or damage to tissue.

In some embodiments, an infusion system includes a monitoring system,sensor system, security for an intravascular catheter, a barrierdressing, a wireless status and alert notification system and adjustmentof infusion pump rate. Other embodiments may include a portion of thecomponents or varying components.

The infusion system monitors tissue conditions for indications of tissueinfiltration, extravasation, phlebitis, and similar afflictions that mayresult as a complication of intravascular infusion.

The infusion system can monitor patients in a hospital, home care, orambulatory care setting when a patient is receiving intravenous therapy.

The infusion system monitors patient tissue non-invasively utilizing oneor more sensing technologies. In one illustrative example, the infusionsystem includes bioimpedance sensing alone. A second illustrativeexample includes bioimpedance and infrared sensing technology with thetwo type of information combined and compared to predetermined valuesfor threshold and pattern analysis.

In an illustrative application, the infusion system is applied to apatient at the initiation of an infusion and remains in placecontinuously through the infusion process. In some embodiments, theinfusion system control unit assembles a condition report and posts thecondition report on a visual display. The display can notify a caregiverof the presence or absence of conditions indicating an infiltration orextravasation. The infusion system can generate an auditory alert signalthat indicates occurrence of the condition.

In accordance with another aspect of the infusion system, biosensors areincluded in the film barrier dressing that are capable of performinganalytic chemistry measurements at the point of care to enable rapidcorrection of electrolyte abnormalities and improved medical care.

Various aspects of the illustrative infiltration detection system may beutilized individually or in combination and are useful to identify anabnormal infusion as early as possible without generating an excessivenumber of false alarms. Aspects include an at least partiallytransparent film barrier dressing, sensors combined into the dressing,parameter modeling using one or more sensing technologies, conditiondetection using pattern recognition, generation of an alarm signal orannunication, generation of signals to control operation of an infusionpump, and others. Early detection allows attending medical staff torectify problems before significant damage occurs due to infiltrationand before the patient has been deprived of a significant amount of theintravenous therapy.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of the described embodiments believed to be novel arespecifically set forth in the appended claims. However, embodiments ofthe invention relating to both structure and method of operation, maybest be understood by referring to the following description andaccompanying drawings.

FIG. 1 is a schematic pictorial diagram that illustrates an infusionsystem with a capability to monitor tissue conditions.

FIG. 2 is a schematic pictorial diagram that illustrates another exampleof an infusion system with a capability to monitor tissue conditions.

FIG. 3 is a pictorial diagram showing an example of a suitable filmbarrier dressing for usage with an infusion system.

FIG. 4 is a schematic pictorial diagram that illustrates top andcross-sectional views of an example of a suitable electrical impedancesensor for usage in an infusion monitoring device.

FIG. 5 is a schematic block diagram illustrating another example of anelectrical signal sensor in the configuration of an electrode arraysensor.

FIGS. 6A and 6B are block diagrams illustrating an example of anadditional electrical signal sensing technology, an electric signaltomogram scanner.

FIG. 7 is a schematic pictorial diagram showing an example of a suitabletemperature sensing device for usage in the infusion system.

FIG. 8 is a schematic pictorial diagram that depicts a suitable opticalsensor for usage with the infusion system.

FIG. 9 is a schematic block diagram illustrating an example of a controlunit suitable for usage with the illustrative infusion system.

FIG. 10 depicts a schematic pictorial view of an example of a controlunit that is configured to be attachable to a patient's arm, IV pole, orother patient's appendage.

FIG. 11 is a flow chart that depicts an example of a technique fordetecting a harmful tissue condition during an infusion.

FIG. 12 is a schematic circuit diagram showing an impedance model oftissue that is useful for describing conductivity reconstruction intissue.

FIG. 13 is a schematic block diagram that illustrates an eight-electrodeconfiguration for a tissue impedance measurement.

FIG. 14 is an Electrical Impedance Tomography (EIT) block diagram.

FIG. 15 is a schematic pictorial diagram showing a Finite Element Method(FEM) mesh.

FIG. 16 is a highly schematic pictorial diagram that depicts sensitivityanalysis using the Jacobian matrix.

FIG. 17 is a flow chart that illustrates an embodiment of areconstruction method for Electrical Impedance Tomography.

DESCRIPTION OF THE EMBODIMENT(S)

Referring to FIG. 1, a schematic pictorial diagram illustrates aninfusion system 100 with a capability to monitor tissue conditions. Theinfusion system 100 can be used to infuse a flowable material or fluidin the form of liquid, gas, or a combination into a patient. Theillustrative infusion system 100 includes an infusion device 110 thatdelivers the infusion fluid and a conduit 112 for conducting the flowingmaterial from the infusion device 110 to the patient. The conduit 112comprises a flexible tubing 114 that couples to the infusion device 110and a cannula 116, such as a needle or catheter, that is capable ofinserting into the patient's vascular system.

The infusion system 100 is a noninvasive system that can be applied tothe surface skin for monitoring in one or more dimensions usingdepth-selective cross sectional surface and subcutaneous tissue overtime in a patient receiving an intravascular infusion to measure andcharacterize tissue conditions. The infusion system 100 can be used todetect and notify an individual of the presence or absence ofphysiological conditions that may indicate tissue complications such astissue infiltration and extravasation during intravascular infusions.

The infusion system 100 also comprises a sensor dressing 118 withsensors 120 integrated into a film barrier dressing 122, a sensor signalpathway 126, and a control unit 124 that controls monitoring, analysis,and notification of tissue condition. The sensor signal pathway 126 canconnect between the film barrier dressing 122 and the control unit 124,carrying data and control signals. The sensor signal pathway 126 can beof any suitable technology including conductive wires, fiberopticchannels, wireless channels, and others.

The film barrier dressing 122 is a tissue-contacting section that iscapable of temporary affixation to surface tissue over one or moretissue sites, typically including an intravascular insertion site. Thefilm barrier dressing 122 protects the skin and tissue in the vicinityof the infusion against exposure to pathogens in the environment,reducing the possibility of infection, and secures the catheter toreduce or eliminate motion that may result in complications. The filmbarrier dressing 122 is transparent or includes a transparent or clearwindow to allow visual of the infusion site and forms a structuralsupport for the sensors 120. The film barrier dressing 122 has one ormore adhesive layers capable of contacting and affixing to patienttissue and also capable of securing a needle or intravenous catheteragainst the skin and sealing the top of an intravascular insertion.

In some embodiments, the film barrier dressing 122 is a tissuecontacting dressing that at least partially attaches to tissue andcontains a polymer adhesive suspended in a neutral protein compound. Theadhesive can be loosened or removed by applying water or alcohol.

The sensors 120 can be of a single type or multiple types and arecapable of detecting signals using one or more sensing technologies.Suitable sensor types include bio-impedance, spectrometry,spectrophotometer, oximeter, photonics, other optical technology,magnetoresistive, micro-electro-mechanical system (MEMS) sensors,acoustic sensors, and others.

In some examples, the sensors 120 contain one or more elements capableof sending and receiving signals from tissue in one or more bodylocations. The sensors 120 comprise one or more sensor arrays adaptedfor transmitting signals into tissue and receiving signals from thetissue using one or more sensing technologies.

In one particular example, the sensors 120 acquire signals using twosensor technologies including a bio-impedance sensor and an opticalsensor. Other embodiments may include only a single sensor, other typesof sensors, or more than two sensors. The bio-impedance sensor isconnected to the control unit 124 via an electrically-conductive sensorpathway and a spectrophotometry sensor is connected to the control unit124 using a fiberoptic light pipeline. The control unit 124 analyzes thebio-impedance information in combination with the spectrophotometricinformation are compared to threshold and/or historical stored values tomonitor tissue for detection and notification of tissue conditions suchas extravasation and infiltration.

In some embodiments, an infusion system 100 utilizes a plurality ofsensing technologies to improve reliability and reduce or eliminate theoccurrences of false alarms. The control unit 124 can utilizeinformation obtained using the multiple sensing technologies, store andanalyze a time history of the information using various techniques suchas thresholding and pattern recognition.

The infusion system 100 can be used to deliver fluid for variouspurposes including patient hydration, nutrient delivery, therapeuticdrug delivery, diagnostic testing, supply of blood components or otherhealthcare materials. During operation, the infusion device 110 deliversinfusion fluid through the flexible tubing 114 and the cannula 116 intothe patient's vascular system.

The infusion system 100 is suitable for use in any suitable IV setting,such as routine patient care in medical surgical units, operating roomambulatory care centers, home healthcare for patients undergoingintravenous therapeutic treatment, and others.

The control unit 124 obtains and stores information from the sensors120. Depending on the particular sensing technology, the control unit124 may include various signal conditioners and processors to configurethe information more suitably for subsequent analysis and storage.

For some sensor technologies such as sensors that acquire electricalinformation in one or more frequency bands, the control unit 124includes a multiple gain amplifier circuit. In one example, theamplifier circuit may have multiple filter stages (not shown) such as ahigh-gain stage, a medium-gain stage, and a low-gain stage connected ina cascade configuration. The cascaded filter is coupled to an analog todigital converter (not shown) that can convert the sensed informationfor analysis and storage under control of a processor (not shown).

The processor may be any suitable type such as a microprocessor, acontroller a microcontroller, a central processing unit (CPU), a digitalsignal processor (DSP), a state machine, discrete logic, or the like.The processor can be programmed to perform a variety of analysis,storage, and control functions. In one example, the processor includes aprogram for generating data images from processed signals that areindicative of tissue condition. The processor also includes a controlprogram for controlling signals acquisition by the sensors 120. Theprocessor may include a communication program for communicatinginformation to a remote location, enabling remote surveillance of tissuemeasurements and characteristics.

The infusion system 100 detects and monitors one or more conditionsincluding blood clots, phlebitis, tissue necrosis, and intravascularinfiltration and extravasation associated with the infusion of aflowable material in a vascular pathway. The infusion system 100, upondetection of one or more particular conditions, can generate a detectionsignal, a status and alarm notification, giving medical surveillance ofthe status of tissue as a patient receives an infusion. The surveillancesignal notifies a health care provider or caretaker to intervene earlyto avoid intravascular complications. The alarm may be an audible sound,a warning screen display for a computer, a vibration or buzzerannunciation, flashing lights, or any other suitable signal. Thenotification signal may be delivered to a proximal or remote location.

The control unit 124 may have an alarm or enunciator that enables acaretaker, for example a nurse, positioned in a remote location tosupervise a patient's infusion. The infusion system 100 can beconfigured as a safe, efficient, inexpensive, and reliable monitoringdevice for early detection of infiltration, extravasation, and othercomplications that is suitable for use both inside and out of a hospitalenvironment. The sensor dressing 118 can be applied at the perivasculararea at the site of the intravascular insertion and also at bodylocations remote from the insertion that are at risk of fluid collectiondue to infiltration and extravasation.

In some embodiments, the control unit 124 is capable of communicatingwith an infusion controller 132 that is a component of the infusiondevice 110 to control an infusion pump 134. The infusion system 100monitors patient tissue condition and, under control of a surveillanceprogram executing in the control unit 124, can detect harmful tissueconditions and reduce complications by adjusting infusion flow orterminate infusion in response to the alarm condition.

Referring to FIG. 2 in combination with FIG. 1, a schematic blockdiagram shows functional blocks of a physiological monitoring system 200for monitoring surface tissue and subcutaneous tissue with a capabilityto monitor tissue conditions. A tissue contacting section 118 contains asensor pathway and is attached to a control unit housing 124 by anumbilical cable 126. A fiber optic line 218 runs inside the umbilicalcable 126 and is connected through the tissue contacting section 118.

Various types of connectors may be used. Several suitable connectortypes include zebra connectors, pin connectors, conductive adhesives, amodified EKG snap that can be snapped onto a tail connector, a Ziffconnector, and others. Circuit connectors may be connected by aninteractive “tail” that exits the dressing either internally orexternally. Connections are commonly made by CTR-CTR DuPont® “clincher”or AMP® “multiple-crimp” connector. Interconnection may also be attainedusing CTR-CTR, PC board-mounted, slide-in, pressure connectors,Elastomeric® “zebra-strip” connectors and “Z-axis-only” conductiveadhesives. The wide range of connection selections address space andcost constraints.

An optical sensing system 210 includes an optical source 212 and anoptical detector 214. The optical source 212 is known to those ofordinary skill in the optics arts and typically includes a time-gatingcircuit, a pulse synchronization circuit, and a gate switch coupled toan infrared generator. The optical detector 214 is known to those havingordinary skill in the optics arts and includes a photonics detectorcoupled to a processor 220 via an analog to digital converter.Information from the optical detector 214 can be shown on a display 216such as a liquid crystal display (LCD) module. Light from the opticalsource 212 is transmitted to the patient's skin via the fiber optic line218 and reflections from the skin are transmitted back to the opticaldetector 214 via the fiber optic line 218. The processor 220 can beconnected to an alert tone generator 222 to inform a caretaker or thepatient of an alert condition.

In the illustrative system, the processor 220 can communicate with avisual screen 224 and pager 226 that are freestanding. A catheter andcable securement support (not shown) can be attached to the tissuecontacting section 118.

A polymer protein coating adhesive, hydrogel adhesives, and conductiveink sensor pathway are applied to the tissue-contacting segment 118. Asilver conductive ink adhesive can be applied in a selectedconfiguration.

A caretaker uses the monitoring system 200 by applying the tissuecontacting segment 118 to the surface of a patient's skin at one or moremonitoring positions, including over the site of intravascularinsertion. A catheter and cable securement support is applied on anintravenous catheter used to deliver infusion material into thepatient's vascular pathway. The umbilical cable 126 attaches to thecontrol housing unit 124. The caretaker can activate the control unit byactuating an on-off switch (not shown).

The infrared generator sends near infrared signals through the infrareddelivery pipeline including the fiber optic line 218. The sensor pathwayfor the optical light could be clear pipelines or free air. The infrareddetector responds to pulse excitations from subcutaneous and surfaceskin. Signals from the infrared detector are monitored utilizing amulti-gain preamplifier circuit (not shown) connected to the outputterminal of a photonics detector. A gate switch (not shown) connected tothe output terminal of the multi-gain preamplifier controls sampling ofthe photonics detector signals. The multigain amplifier circuit connectsto an integrator (not shown) to integrate the acquired samples.

A time-gating circuit connected to a switch opens and closes the switchat regular time intervals during signal monitoring. The pulsesynchronization circuit connected to the time-gating circuit supplies asignal to the time-gating circuit that indicates when the pulse isexpected to arrive at the photonics detector. Data from the opticaldetector 214 are collected, compared to control information, quantified,and analyzed to determine the presence or absence of conditions that mayindicate infiltration and extravasation.

The physiological monitoring system 200 may also include a bio-impedancesensing system 230. The bio-impedance sensing system 230 furthercomprises a current generator 232 and an ampere meter 234. The currentgenerator 232 sends current through the hydrogel conductive sensorpathway to the tissue while an ampere meter 234 records data using ananalog to digital converter (ADC) and sends the information to theprocessor 220. In another example the conductive pathway can be formedby small conductive silver wires. The processor 220 stores data,compares the data with preset information including threshold andpatterns to determine the presence of absence of conditions that mayindicate infiltration or extravasation.

The processor 220 combines the bio-impedance and optical information andforwards information on tissue condition by a wireless interface card,for example, to one or more display screens. The display screens mayinclude screens on a pager, a control unit visual display screen, acomputer visual display screen and the like. In one example, informationcan be web enabled and sent via the Internet to a caregiver via personaldigital assistant (PDA).

The hydrogel sensor conductive pathway uses adhesives of hydrogelconductive ink 238 to couple the tissue contacting segment 118 totissue. In a specific example, the adhesive is an adhesive of silverconductive ink.

The monitoring system can be configured as a highly reliable,lightweight, and economical device for monitoring the tissue conditionsand identifying complications that may occur during infusion. Acaretaker receives useful information to improve quality of patient carein the hospital, home care setting, chemotherapy clinic, or at anylocation.

Referring to FIG. 3, a pictorial diagram shows an example of a suitablefilm barrier dressing 300 for usage with an infusion system. The filmbarrier dressing 300 is a flexible membrane can be temporarily attachedto a patient's skin and later removed. The film barrier dressing 300 canbe constructed from several flexible membrane materials such asbreathable barrier films that supply moisture vapor permeability whilepreventing passage of liquids through the dressing. Typical flexiblemembrane materials include microporous materials and dense monolithicmembranes. Some of the membrane materials are useful for infectioncontrol and pass water vapor while excluding or killing pathogenicmicroorganisms such as bacteria.

A microporous structure has capillary-like pores that inhibit liquidflow due to the small size of the pores and lyophobicity of the polymermembrane material. Gases and vapors permeate a microporous film byphysical mechanisms based on pore size. If the diameter of the holes isless than the mean free path of the gas, individual molecules can passbut bulk gas flow is prevented. Physical structure rather than polymerchemistry determines permeability of microporous films, in contrast todense monolithic membranes.

A dense monolithic membrane functions as an absolute barrier to liquidbut has selective permeability to gases and vapors. The dense membranesare pinhole-free polymer membranes that transmit vapors andnoncondensable gases through activated diffusion resulting fromconcentration gradients within the membrane. Suitable polymers includenonpolar, nonhygroscopic polymers such as polyethylene andpolypropylene. Permeability is increased for variations in chemistry orstructure that increase diffusion constant and permeability.

Suitable barrier membrane materials include film dressings from TycoHealthcare—U.S. Surgical of Norwalk, Conn., Tegaderm™ and padtransparent dressing from 3M of Minneapolis, Minn., and dressings fromProtein Polymer Technologies, Inc. of San Diego, Calif. , transparentfilms that function in the manner of artificial skin. For example,suitable film dressings are secure dressings that are transparent forviewing the puncture site and condition of surrounding skin, whilepreventing proliferation of bacteria.

The film barrier dressing 300 has a laminar structure comprising, forexample, a base film 312, an adhesive layer 314 coupled to anapplication side of the base film 312 and a foam layer 316 coupled tothe base film surface opposite the adhesive. Coupled to the foam layer316 is a conductive ink layer 320 that is patterned to form electricallyconductive lines. In one example, the conductive ink is composed ofsilver/silver chloride although other conductive materials may be usedincluding carbon, gold, electrically conductive composites, metallics,conductive polymers, foils, films, inks, or any forms of thermistorcatheters. Other suitable conductive materials include wires, platinum,aluminum, silicone rubber conductive materials with nickel-graphitecompounds, nanopowders and proteins, graphite conductive wires, and thelike. A dielectric insulator 321 separates the conductive ink layer 320in a selective manner and prevents migration of conductive materials.

A hydrogel layer 322 overlies the foam layer 316 and the patternedconductive ink layer 320. A film release liner 324 is coupled to thehydrogel layer 322 for application of the film barrier dressing 300 tothe patient's skin. A plurality of electrodes 330 are patterned in theconductive ink and also in conductive portions of the adhesive andintegrated hydrogel to make contact with the patient's skin. Theconductive ink layer 320 is patterned to form conductive lines in thefilm barrier dressing 300 that extend to a terminal strip 334 withcontacts 336 for connecting to communication lines in a cable forcommunicating with a control unit. In one example, the control unitcommunication lines electrically connect to the contacts 336 using aclip 338 containing terminals capable of supplying an energizing signalto the electrodes 330. A connecting pad (not shown) in combination withthe dielectric insulator 321 supply insulation and protection againstmigration of conductive material in the cable containing the conductivecircuit and at a junction of the connecting pad and the cable.

In some embodiments, the film barrier dressing 300 utilizes a conductiveink layer 320 in which a silver conductor is cured on a material thatcan be affixed to tissue. The silver conductor is screen printed on aflexible material. The silver conductor can utilize a polymer thick filmcomposition such as polyester, polyamide, polycarbonate, and epoxyglass. The silver chloride ink is ink printed on the sensor systemmaterial.

The film barrier dressing 300 includes a frame 310 and a flexibleprotective film 332. In the illustrative example, the frame 310 extendsalong peripheral edges of the film barrier dressing 300 leaving aninterior void, and the flexible protective film 332 is attached to theframe 310 and extends over the interior void. The electrodes 330 may beformed in the frame 310, the flexible protective film 332 or both.

The interior void is typically sufficiently large to allow visualizationthrough the patient's skin. The frame 310 can be composed of anymaterial with suitable flexibility, strength, and hygienic properties. Asuitable frame material is Melinex from Tekra Corporation of New Berlin,Wis. Although the frame 310 is depicted as rectangular in geometry, anysuitable shape may be used including circular, oval, triangular, or anyother shape. The electrodes 330 are typically configured as two or moreelectrode pairs. For example, so that alternating electrical energy maybe applied to a first pair of electrodes to generate an electric fieldto induce a signal in a second electrode pair. The generated field is afunction of the impedance of the tissue.

The electrodes 330 can be flexibly formed in various suitableconfigurations to facilitate detection of selected signals. Theelectrodes 330 can be patterned in selected shapes by laminatingalternating planes of conductive ink layer 320 and layers of dielectricinsulator 321. For example, conventional semiconductor laminatingtechniques can be used to form electrodes 330 of desired geometries. Insome particular examples, coil electrodes can be manufactured byselective patterning of multiple layers, with individual layers having apatterned conductive ink layer 320. Overlying and underlying patterns inthe conductive ink layer 320 form the coils. Coil electrodes generate afavorable current density distribution for electrical measurements. Coilelectrodes commonly interrogate in a frequency range of 1 MHz to 10 MHzto attain good depth sensitivity. In contrast contact electrodesgenerally operate in a frequency range from about 10 kHz to 100 kHz. Invarious systems, the coils may have different configurations. Some coilsare contact coils that are placed in contact with the skin, other coilsare noncontact coils that are removed from the skin by a predetermineddistance.

A control unit communicates with the electrodes 330 in the film barrierdressing 300 to gather and process information for determining tissueimpedance. The control unit determines the occurrence of extravasationanalyzing tissue impedance measurement patterns in time and space,thereby enabling early detection.

In an example of a tissue impedance measuring operation, a caretakeraffixes the film barrier dressing 300 so that the electrodes 330 enclosethe tip of the needle or catheter and extends up to approximately threeinches. The extended film barrier dressing 300 can monitor tissue in thearea of the insertion site of the vascular access device and surroundingperivascular tissue. The control unit applies a voltage across a firstpair of electrodes to induce a signal in a second pair of electrodes andmeasures impedance at the second pair of electrodes. The control unitstores the impedance measurements over time and determines changes inthe impedance from a baseline measurement taken prior to commencing theinjection procedure.

The infusion system is typically used to detect IV complications byintroducing a cannula or needle into the patient's vascular system,removing the film release liner 324 and attaching the film barrierdressing 300 to the patient's skin using the adhesive layer 314. Thefilm barrier dressing 300 is positioned so that the needle tip iscovered by the void interior to the frame 310.

The film barrier dressing 300 functions as a securement system that isadaptable to cover a suitable size area of tissue. In one example, thefilm barrier dressing 300 is a flexible material that is adaptable tocover an area of approximately 1×1 inch or extendable to approximately3×8 inches. Typically, the smaller patch can be used to monitor at theinfusion site and the larger patch can be used at any suitable locationon the body.

In some embodiments, the film barrier dressing 300 may include a polymerdelivery system with a topical antiseptic applied for delivering topicalantibiotics. The topical antiseptic is delivered over time withelectrical current applied to the electrodes to enhance antibioticdelivery and increase penetration of the antibiotic through the skin.

In a specific example, a dressing may include lidocaine for topicalapplication. In some systems, the antiseptic may be applied to thedressing prior to application to the patient's skin, for example, as amanufacturing step. In other systems, the dressing is applied to thepatient's skin without the antiseptic so that baseline sensormeasurements may be acquired. The antiseptic may then be applied laterto better track changes that result from the therapy.

Referring to FIG. 4, a schematic pictorial diagram illustrates anexample of a suitable electrical signal sensor 400 that is capable ofmeasuring bio-potentials, bio-impedances, electrical impedances, and thelike for usage in an infusion monitoring device. The illustrativeelectrical signal sensor 400 is a plethysmograph that can be applied toa patient's appendage to detect extravasation, infiltration, phlebitis,or other conditions during injection of fluid into the patient's bloodvessel. Typically, an electrical impedance sensor 400 is positioned sothat the geometric center of multiple sensor elements corresponds to thelocation of the injection site.

The illustrative electrical impedance sensor 400 has six electrodes 410.Other examples of a suitable sensor may have fewer electrodes or moreelectrodes. The electrodes 410 may be constructed from a silver/silverchloride mixture or other suitable conductive material. The illustrativeelectrodes 410 include three stimulating electrodes 418 and threereceiving electrodes 416.

The electrodes 410 can be positioned, if possible, in direct ohmiccontact with the patient's skin or, otherwise, capacitively coupled witha slight offset from the skin in the vicinity of the injection site.

The electrical impedance sensor 400 includes a current source 412 forapplying a current to the injection site via the stimulating electrodes410 and a high impedance amplifier 414 that is connected to the tworeceiving electrodes 410 and receives and amplifies the voltagedifference between the receiving electrodes 416. The current source 412typically injects radio frequency (RF) energy in a suitable range offrequencies, for example from one kilohertz to about one megahertz.

Extravasation causes a volume change due to tissue swelling and aconductivity change which, in combination, change the electricalimpedance sensed by the receiving electrodes 416. An impedance variationmodifies the voltage detected by the high impedance amplifier 414,permitting extravasation detection, notification of IV complications ofinfiltration, extravasation, and other conditions, and intervention, forexample by terminating IV application.

The electrodes 410 can be positioned on the surface of a high dielectriclayer (not shown) to attain efficient capacitive coupling to thepatient. A hydrogel layer (not shown) coupled to the high dielectriclayer on the surface for application to the patient's skin may be usedto improve electrical coupling of the electrodes 410 to the patient.

A low dielectric layer (not shown) coats the electrodes 410 and the highdielectric layer and functions as a substrate for applying theelectrodes 410 to the patient. A high conductivity layer (not shown)coats the low dielectric layer and functions as a ground plane for theelectrical impedance sensor 400 that shields the electrodes 410 fromstray capacitance, improving impedance measurement reliability.

Although the illustrative electrical impedance sensor 400 has sixelectrodes 410, additional electrodes may be added in variousconfigurations to attain additional functionality. For example, thesix-electrode electrical impedance sensor 400 may be more suitable fordetecting extravasation and infiltration in the vicinity of the infusionsite and collection of fluid due to dependent edema. Additionalelectrodes may be added to detect extravasation and infiltration at aposition remote from the insertion, for example due to valve disease orweakening of vessel walls. The additional electrodes in combination withthe electrodes 410 may be arranged in various configurations to extenddiagnostic performance. Alternatively, additional electrical impedancesensors may be used to detect remote extravasation. For example, theelectrodes may be arranged in an annular array configuration or a lineararray configuration. In one example, two outer electrodes may beconnected as a source and sink of RF current, while any two electrodespositioned between the source and sink can be used to measure current,voltage, or impedance. Switches and processing electronics (not shown)can be used to sample from selected inner electrodes to senseextravasation and infusion at multiple positions along the bloodvessels.

In some embodiments, sampling of various positions may be modified overtime to sample predominantly in the vicinity of the injection in theearly IV stages and to sample to detect remote extravasation in laterstages when more likely to occur.

The electrical impedance sensor 400 is useful for monitoringintravascular infiltration and extravasation. Intravascular infiltrationand extravasation may alter histological and biochemical tissueconditions in intracellular and extracellular fluid compartments, cellmembrane surface area, macromolecules, ionic permeability, andmembrane-associated water layers. The histological and biochemicalchanges within the infiltrated tissue or area of infiltration andextravasation result in a measurable change in tissue electricalimpedance.

In some embodiments, the electrical impedance sensor 400 comprises aplurality of transducers to generate one or more sensor pathwaysutilizing depth-selective sensing of tissue bio-impedance in a desiredfrequency range. The bio-impedance sensor 400 generates cross-sectionalsurface measurements and subcutaneous measurements at one or moreselected tissue depths by controlling the field extension of the sensorpathway. Interrogation of various depths occurs by sampling atelectrodes positioned at multiple locations, using electrodesconstructed from various different materials, interrogating using amultiple array transducer configuration, and interrogating at variousselected frequencies or with various selected interrogation waveforms.

In a particular example, the electrical impedance sensor 400 fastreconstruction technique applies currents to the body surface andmeasures resulting surface potentials. The fast reconstruction techniquepresumes that a linear dependence exists between the small deviation inimpedance and the corresponding change of surface potentials. Thegeometry of the internal organs or tissue is known so that initialconductivity estimates are presumed known. A sensitivity matrix encodesthe presumed impedance values and conductivity changes are found byinverse-matrix multiplication.

Under processor control, the electrical impedance sensor 400 appliescurrents to selected electrodes on the body surface and measuresresulting surface potential distributions from the electrodes. Thesensitivity matrix A describes the dependence between small deviationsof conductivity and a change of measured surface potentials according toequation (1) in which Δσ is the vector of the individual conductivitydeviations and Δφ describes changes of measured surface potentials:Δφ=A·Δσ  (1)

Knowledge of the sensitivity matrix for a model organ or tissue geometryand electrode arrangement permits determination of conductivitydeviations according to equation (2) in which A⁻¹ is the pseudoinverseof matrix A determined using singular value decomposition:Δσ=A ⁻¹·Δφ  (2)

The sensitivity matrix A can be determined by simulating measurementsusing conductivity values obtained from literature or experiment. Insome applications, conductivity values can be gradually changed andsurface potential distributions can be measured for the differentconductivity values to determine the column values for the matrix. Inalternative examples, sensitivity can be directly calculated using amore efficient finite element analysis discussed hereinafter withrespect to FIGS. 12 to 17.

The electrode pattern and position are selected for the particulartested organ or tissue, depending on the geometry and conductivitydistribution of normal and abnormal tissue, and optimized to generatethe maximum voltage difference between the normal and abnormal case.

The electrical impedance sensor 400 includes multiple sets of electrodesand the pattern of excitation current and electrode shape and positionis defined based on application. The electrical impedance sensor 400 isconfigured to recognize objects in a formal known position according toconductivity data measured for normal tissue. Accordingly, testmeasurements of current density distribution in normal and abnormalcases are stored and compared with test measurements to classify thetissue under test.

Some embodiments may use one large electrode and a plurality of smallelectrodes. Measurements may be made at one or more test frequenciesdepending on the impedance frequency spectrum of the measured tissue.Pattern recognition is made based on modeling of electric fields andcurrent density using sensitivity analysis for pattern recognition inthree dimensions and finite element analysis. In various embodiments,linear inversion or nonlinear inversion may be used for patternrecognition.

In some embodiments, a control unit obtains and compares thebio-impedance measurements to measurements acquired using a secondtechnology. For example, an optical sensor can be used to detect a lightreflection pattern generated by an infrared light source. Otherembodiments may use only a single measurement technology.

In another example of a fast bioimpedance tomography technique, tissueimpedance maps are constructed from surface measurements using nonlinearoptimization. A nonlinear optimization technique utilizing known andstored constraint values permits reconstruction of a wide range ofconductivity values in the tissue. In the nonlinear system, a JacobianMatrix is renewed for a plurality of iterations. The Jacobian Matrixdescribes changes in surface voltage that result from changes inconductivity. The Jacobian Matrix stores information relating to thepattern and position of measuring electrodes, and the geometry andconductivity distributions of measurements resulting in a normal caseand in an abnormal case. The objective of the nonlinear estimation is todetermine the maximum voltage difference in the normal and abnormalcases.

In another example of a sensing technology using bio-potentialmeasurements, the electrical signal sensor 400 may measure the potentiallevel of the electromagnetic field in tissue. A suitable bio-potentialsensor includes a reference electrode and one or more test electrodes.In some systems, the test and reference electrodes may beinterchangeable, for example under control of a processor, to vary thedesired tissue measurement field.

The sensor may be any suitable form of electrode 410. In one example,the electrodes 410 are predominantly composed of a silver chloride(AgCl) layer coupled to an electrode lead by a silver (Ag) layer. Thetissue contact surface of the electrode is a concentrated salt (NaCl)material coupled to the AgCl layer. The electrode may also include aninsulated housing that covers the AgCl layer, the Ag layer, and the endof the lead to reduce electromagnetic interference and leakage.

The patient's tissue generates an electromagnetic field of positive ornegative polarity, typically in the millivolt range. The sensor measuresthe electromagnetic field by detecting the difference in potentialbetween one or more test electrodes and a reference electrode. Thebio-potential sensor uses signal conditioners or processors to conditionthe potential signal. In one example, the test electrode and referenceelectrode are coupled to a signal conditioner/processor that includes alowpass filter to remove undesired high frequency signal components. Theelectromagnetic field signal is typically a slowly varying DC voltagesignal. The lowpass filter removes undesired alternating currentcomponents arising from static discharge, electromagnetic interference,and other sources.

Another example of a sensing technology employs noninvasivedepth-selective detection and characterization of surface phenomena inorganic and biological material by surface measurement of the electricalimpedance of the material where the device utilizes a probe with aplurality of measuring electrodes separated by a control electrode. Moreparticularly, the impedance sensor comprises a measuring electrode 412structure with triple annular concentric circles including a centralelectrode, an intermediate electrode and an outer electrode. Allelectrodes can couple to the skin. One electrode is a common electrodeand supplies a low frequency signal between this common electrode andanother of the three electrodes. An amplifier converts the resultingcurrent into a voltage between the common electrode and another of thethree electrodes. A switch switches between a first circuit using theintermediate electrode as the common electrode and a second circuit thatuses the outer electrode as a common electrode.

The sensor selects depth by controlling the extension of the electricfield in the vicinity of the measuring electrodes using the controlelectrode between the measuring electrodes. The control electrode isactively driven with the same frequency as the measuring electrodes to asignal level taken from one of the measuring electrodes but multipliedby a complex number with real and imaginary parts controlled to attain adesired depth penetration. The controlling field functions in the mannerof a field effect transistor in which ionic and polarization effects actupon tissue in the manner of a semiconductor material.

With multiple groups of electrodes and a capability to measure at aplurality of depths, the sensor has a capability of tomographic imagingor measurement, and/or object recognition. Other implementations thatuse fewer electrodes and more abbreviated, fast reconstruction techniqueof finite-solution pattern recognition, can be constructed in smaller,more portable systems. Conventional tomography techniques arecomputation intensive and typically require a large computer. Althoughthese computation intensive techniques can be used to implement thedisclosed system, other techniques with a lower computation burden maybe used, such as the fast reconstruction technique. The fastreconstruction technique reduces computation burden by utilizing priorinformation of normal and abnormal tissue conductivity characteristicsto estimate tissue condition without requiring full computation of anon-linear inverse solution.

Referring to FIG. 5, a schematic block diagram illustrates anotherexample of an electrical signals sensor in the configuration of anelectrode array sensor 500. The electrode array sensor 500 is useful forsensing techniques including impedance, bio-potential, orelectromagnetic field tomography imaging of tissue. The electrode arraysensor 500 comprises an electrode array 510 is a geometric array ofdiscrete electrodes. The illustrative electrode array 510 has anequal-space geometry of multiple nodes that are capable of functioningas sense and reference electrodes. In a typical tomography applicationthe electrodes are equally-spaced in a circular configuration.Alternatively, the electrodes can have non-equal spacing and/or can bein rectangular or other configurations in one circuit or multiplecircuits. Electrodes can be configured in concentric layers too. Pointsof extension form multiple nodes that are capable of functioning as anelectrical reference. Data from the multiple reference points can becollected to generate a spectrographic composite for monitoring overtime

In an illustrative example, the electrode array 510 is configured tofunction as one or more measurement channels. An individual channelincludes one or more electrodes that supply current to the tissue at aselected frequency and selected waveform morphology. Another electrodein the channel is a sensing electrode that senses the voltage generated.

Alternatively, the array may take any suitable form including arectangular, square, circular, oval, triangular, or any othertwo-dimensional shape. The array may include peripheral array elementswith central elements omitted, or take any shape with any patterns ofinner or peripheral elements omitted.

Electrode spacing configurations are predetermined according to thespatial frequency of the detected electric field potential.

Spatial tomography imaging of tissue using detected electricalparameters generally involves spatial deconvolution of detected signalsto reconstruct electrophysiological patterns from detected surfacesignals.

Individual electrodes in the electrode array 510 are coupled to a signalconditioner/processor including preamplifiers 512 for high gainamplification at high input impedance, low current loading, and lownoise. The preamplifiers 512 may be configured to function as a bandpass filter or the signal conditioner/processor may include a band passfilter 514 to confine signals to a desired frequency band. Band passfiltered signals are applied to a multiplexer 516 that can be part ofthe signal conditioner/processor to sequentially sample amplified andfiltered analog signals from individual electrodes in the electrodearray 510.

Analog signals from the multiplexer 516 are digitized by an A/Dconverter 518 that sequentially samples signals from the individualelectrodes of the electrode array 510.

Digital signals from the A/D converter 518 can be applied to a processor520 for analysis, storage 522, and/or display 524. The processor canexecute a variety of functions such as computing a spatial deconvolutiontransformation of detected electrode field potentials.

In another example of the electrode array sensor 500, the electrodes canbe arranged as one or more sets of electrode groups. An electrode groupincludes three pairs of electrode. A first electrode pair is excitationelectrodes, a second pair is sensing electrodes, and a third pair isfocusing electrodes. The focusing electrodes focus current flowingbetween the excitation electrodes to the sensing electrode region.

The excitation electrodes and the sensing electrodes are spaced so thatthe sensing electrodes are capable of measuring the voltage drop betweenthe sensing electrodes that occurs as a result of an excitation pulse atthe excitation electrodes. The focusing electrodes focus the currentflowing between the excitation electrodes to the sensing electroderegion. In one example, the focusing electrodes are planar electrodes,aligned and on opposite sides of the line between the two excitationalelectrodes.

Referring to FIGS. 6A and 6B, block diagrams illustrate an example of anadditional electrical signal sensing technology, an electric signaltomogram scanner 600 that may be used in embodiments with extensivecomputation capabilities. Other implementations that use moreabbreviated fast reconstruction technique of pattern recognition, can beconstructed in smaller, more portable systems. The electric signaltomogram scanner 600 comprises a signal generator 610, a plurality ofboundary condition modules 612, a plurality of data acquisition modules614, and an electrode array 616. The electric signal tomogram scanner600 receives control signals from a processor via an interface 618. Thesignal generator 610 supplies signals to the boundary condition modules612 that communicate with corresponding data acquisition modules 614 todrive the electrode array 616. A data acquisition module 614 drives aplurality of electrode elements in the electrode array 616. A particularcombination of a boundary condition module 612 and a data acquisitionmodule 614 generates boundary conditions and measures resultant voltagedrops across small sensing resistors (not shown) to measure electricalsignals at the individual electrodes in the electrode array 616.

The signal generator 610 supplies a sinewave voltage of suitablefrequency, for example between 100 Hz and 1 KHz to a multiplying digitalto analog converter (DAC) 620, generating a voltage drop across resistor622 and instrumentation amplifier 624 in a data acquisition module 614.

In one example, the signal generator 610 comprises a crystal-controlledoscillator (not shown) coupled to a frequency divider (not shown) thatreduces the oscillator frequency. The frequency divider is in turncoupled to a phase splitter (not shown) that produces a further dividedsignal as one-quarter cycle displaced square waves. The phase splittersupplies the quarter-cycle displaced square wave signals to a delay line(not shown) and to a high Q bandpass filter (not shown). The bandpassfilter is coupled to a buffer amplifier (not shown) to generate asinewave signal p sin 2ft where f is the square wave frequency. Anin-phase squarewave, a quadrature squarewave and subconjugates aredelayed by the digital delay line to compensate for delay through thebandpass filter and the buffer amplifier. Four phases of the sinewaveoccur at positive transitions of the squarewave signals and passed tothe interface 618.

A sample and hold circuit 626 receives the amplified signal and suppliessamples to an analog to digital converter (ADC) 628, timed according toclock signals from the signal generator 610. ADC 628 supplies digitalsignals indicative of current measurements at the electrode in theelectrode array 616.

Electrodes receive a boundary condition that establishes a voltageacross the resistor 622. The data acquisition modules 614 first producea controlled voltage at electrodes in the electrode array 616 toestablish a boundary condition, then measure resulting voltages toenable boundary current computation.

In some embodiments, a processor controls the electric signal tomogramscanner 600 to apply a voltage distribution over some external boundaryof an object and find the current flow at the boundary from a solutionof Laplace's equation to reconstruct the distribution of electricalproperties within the object. The process involves positioning athree-dimensional electrode array 616 about the object, applyingselected voltages to a selected first set of electrodes and measuringcurrents through a selected second set of electrodes, which may includesome or all of the first set.

The electric signal tomogram scanner 600 imposes a virtualthree-dimensional grid onto the object at a selected resolution levelwith each node of the grid allowed to assume an independent electricalparameter. The scanner determines a best value for the electricalparameter for each node without any preconditions. The electric signaltomogram scanner 600 then performs an iterative process to determine aspecific distribution of electrical properties at the grid nodes to mostclosely match the measured currents at the boundary and the currentsbased on the specific distributions.

In the illustrative electric signal tomogram scanner 600, the boundarycondition modules 612 and the data acquisition modules 614 are identicalexcept that the boundary condition modules 612 store preset boundaryconditions in a nonvolative memory.

Referring to FIG. 7, a schematic pictorial diagram shows an example of asuitable temperature sensing device 700 for usage in the infusionsystem. The illustrative temperature sensing device 700 is a biomedicalchip thermistor assembly that is useful both for intermittent andcontinuous monitoring. The thermistor 700 includes a stainless steelhousing 710 that is suitable for reusable and disposable applicationsand has a nominal resistance value that ranges from approximately 2000Ωto about 20,000Ω at 25° C. The thermistor body 712 including wires 714and sensor tip 716 can be composed of stainless steel. The wires 714 areinsulated using a suitable material such as medical grade PVC teflon. Inother examples, the body material can be composed of materials such aslexan for the wires 714 or shaft and an aluminum tip, or molded plasticor kapton. Other suitable insulating materials include teflon, heavyisomid, or polyurethane with a nylon coat. The thermistor 700 is anelectrical circuit element that is formed with semiconducting materialsand is characterized by a high temperature coefficient. The thermistor700 functions as a resistor with a temperature coefficient rangingtypically from about −3 to −5%/° C. The thermistor can be activatedusing either current or voltage excitation. The thermistor 700 isconnected via the wires or shaft to a high resolution analog to digitalconverter. Thermistors are non-linear devices so that linearizationtechniques are typically used to obtain accurate measurements.

Referring to FIG. 8, a schematic pictorial diagram depicts a suitableoptical sensor 800 for usage with the infusion system. In one example,the optical sensor 800 is an infrared light emitting diode(LED)/phototransistor pair that can sense detectable variations in skincharacteristics. The optical sensor 800 comprises an emitter or infraredtransmitter (LED) 810 and a photonics or retrosensor detector 812 thatmeasure light reflections to derive data points. When gently pressedagainst the skin radiation from the transmitter 810 through across-section of tissue including surface and subcutaneous tissuereflects back into the detector 812. Retrosensor detector 812photocurrent detects the infrared signal and produces an ac signalacross transistors Q2 and Q3 of about 500 uV peak to peak for a 1%change in skin reflectance, a logarithmic relationship that is constantover many orders of photocurrent magnitude. Therefore reliable circuitoperation is possible despite wide variation in skin contrast and lightlevel. Signals from the transistors Q2 and Q3 are applied to a high-gainadaptive filter 814 that rejects ambient optical and electrical noiseand supplies a clean signal to comparator 816 to extract a digitalsignal.

Referring to FIG. 9, a schematic block diagram illustrates an example ofa control unit 900 suitable for usage with the illustrative infusionsystem. The control unit 900 is contained in a housing (not shown) andattaches to one or more sensors 910, 912, and 914 for detecting variousphysiological signals. Although the illustrated example depicts threesensors, a single sensor or any suitable number of sensors may beimplemented depending on the particular parameters to be sensed for anapplication. One example of a suitable system includes a bio-impedancesensor 910, an optical sensor 912, and an ultrasound sensor 914. Othertypes of sensors may replace the illustrative sensors or be used inaddition to the illustrative sensors. Other suitable sensors include,for example, a flow sensor that senses infusion fluid flow, a pressuresensor, a thermistor, thermometer or other temperature sensing device.

In some embodiments, biosensors can be incorporated into layers of theflexible dressing material. For example, Dupont Microcircuit Materialsof Research Triangle Park, N.C. Biosensor materials can be incorporatedinto the flexible dressing material layers in various geometries usingscreen printing of conductive inks. Note that other embodiments mayutilize more conventional die-cut foils. The conductive inks are highlysuitable and permit high-speed, high-volume production usingcommercially-available production equipment.

The conductive inks are typically silver, gold, and carbon inks composedof thermoplastic polymer-based materials that are screen printed anddried or cured. When the ink is dried and all solvent is removed, theprinted area becomes electrically conductive or insulative. The inkscarry electrical current from a power supply to an active area of thebiosensor. Cured inks have useful properties of low resistivity and thushigh conductivity permitting low voltage applications, flexibility, andadhesion.

Because the different inks have varying resistivities, for example goldhaving a lower resistance than silver, which has lower resistance thancarbon, the inks can be selected to achieve selected circuitperformance. Carbon ink can be used as an overprint for silver inks toprevent silver migration from two adjacent traces that carry differentamounts of current or potential, achieving a battery effect.

The conductive inks are highly adhesive to various substrate materialssuch as polyester, or Cetus fabric, a polyester substrate supplied byDynic USA Corporation of Hillsboro, Oreg. Cetus is typically a whitebacking material for the flexible dressing, upon which silver conductiveink can be printed. Other suitable substrate materials includePolyester, Mylar or Melarax. Printable inks are suitable for usage on apolyester substrate that is print-treated and heat-stabilized.

Polymer thick film (PTF) inks contain a dispersed or dissolved phase andattains suitable final properties simply by drying. When printed andcured on a substrate, a particular electronic or biologicalfunctionality develops in the dried film. Suitable substrate includepolyester films such as DuPont TeijinT Mular® or Melinex®, or ceramicGreen TapeT. PTF products applied to flexible substrates are compact,lightweight, environmentally friendly, inexpensive, and permit efficientmanufacturing techniques. PTF films can be folded, twisted, bent aroundcorners, or bonded to any surface, permitting flexible application. PTFfilms are suitable for small features and layers can be printed inlayers to develop multiple functions. Polymer thick film technology ishighly suitable for printing electrodes and other components ofdisposable biosensors.

The conductive inks are flexible to prevent creasing that can increaseelectrical resistance or cause cracking or delamination of the dressingwhen stretched. The flexible dressing material in combination with theconductive ink conforms to the body and allows stretching withoutbreaking the electrodes or increasing electrical noise.

Silver/silver chloride (Ag/AgCl) inks are used to deliver drugs oranesthetic through the skin using iontophoresis. The resistance ofsilver/silver chloride inks used for the electrodes is typicallyselected to be higher than the silver inks used for electricalconnections to restrict the current flowing through the electrodes tolow levels suitable for iontophoresis and to facilitate control ofiontophoresis. Printing selected amounts of the ink directly over silvertraces controls the resistance of silver/silver chloride inks. Thedesired surface area, iontophoresis rate, and duration of drug deliveryare taken into consideration in selection of the size and thickness ofAg/AgCl traces. The stability and reactivity of the drug and/or size ofthe drug molecule determine applicability for iontophoresis sinceinterstitial areas between skin cells can only be expanded to a limitedpoint with electrical current before irritation occurs.

Other sensors, ampermetric sensors, can be incorporated into theflexible dressing to measure concentration of various substances such asglucose, carbon dioxide, oxygen, and others. For example, a glucosesensor incorporates an enzyme into the dressing that reacts withextracted metabolic analytes such as glucose. The reaction creates asmall electrical charge that is proportional to the metabolic reactionrate An electrode indicates the electrical charge and a sensing circuitconverts the electrical charge to a numeric value that can be displayed,analyzed, stored, or the like. The flexible dressing typically includesa hydrogel that stores the enzyme or reagent. The sensor can functionusing reverse iontophoresis in which silver (Ag) ions move from anode tocathode extracting the metabolic analyte from the body and collected ina hydrogel pad. An electrode, for example a platinum-based electrode,can be used to read the current and function as a catalyst to drive thereaction between enzyme and glucose. Some ion-selective permeabilityinks also include a carbon component.

Other sensors, for example potentiometric sensors or electrochemistrysensors, can be used to test electrolytes for example potassium (K) andother selective ions. Inks for sensing electrolytes typically includecarbon with a platinum catalyst reagent as an ion selective sensor.Potentiometric sensors measure the voltage gradient across a metabolicsample according to the sample's level of conductivity at a selectedvoltage according to a calibrated standard. The lower the conductivityof the sample, the higher the voltage for delivering a particular fixedcurrent. Some potentiometric sensors use an ion-selective membrane inkprinted over the electrodes to filter other analytes that contribute tohigh background noise.

Dielectric or encapsulant inks are insulators that protect adjacenttraces from short-circuiting. The dielectric or encapsulant inks alsoassist adhesion. Some dielectrics can be used as capacitors to createcircuits in combination with resistors formed by various resistive inksinside the dressing. Capacitors within the dressing facilitate storageand release of electric current pulses. Ultraviolet dielectrics can beused to define active sensing areas of an electrode, limiting thesurface area of blood or analyte to a selected size.

In other examples, the sensors may include biosensors composed ofnanostructured porous silicon films. Film biosensors detect analytebinding processes using a silicon-based optical interferometer. Thenanostructured porous silicon films are prepared by an electrochemicaletch of single crystal silicon substrates. The biosensor samples areprepared so that the porous silicon films display Fabry-Perot fringes intheir white-light reflection spectrum. Biological molecules arechemically attached as recognition elements to the inner walls of theporous silicon matrix. The film is exposured to a complementary bindingpair, causing binding and resulting in a shift in Fabry-Perot fringes.Analyte binding may be indicative of infiltration or extravasation.

The individual sensors 910, 912, and 914 may be connected withcorresponding respective signal conditioners or processors 916, 918, and920 in the control unit 900. In the illustrative example, thebio-impedance sensor 910 is coupled to a bio-impedance signalconditioner/processor 916, the optical sensor 912 is coupled to aninfrared signal conditioner/processor 918, and the ultrasound sensor 914is coupled to an ultrasound signal conditioner/processor 920. Althoughthe illustrative example, depicts sensors that are respectively coupledto particular signal conditioners or processors, in other examples twoor more sensors may share a particular signal conditioner/processor. Insome examples, a signal conditioner/processor may be dedicated to aparticular sensor and also use other signal conditioners/processors thatmay be shared among sensors. For some sensors, the signal from thesensor is suitable without processing or conditioning so that no signalconditioner/processor is utilized.

In the illustrative example the sensors 910, 912, and 914 and the signalconditioners or processors 916, 918, and 920 are analog sensors andconditioner/processors so that the signals from the signal conditionersor processors 916, 918, and 920 are applied to an analog to digital(A/D) converter 922 to convert the analog signals to digital form. Inother examples, one or more of the sensors or conditioner/processors maygenerate digital signals, bypassing the A/D converter 922. The signalconditioners or processors 916, 918, and 920 may include or omit variouselements such as amplifiers, filters, switches, and the like.

Digital signals from the A/D converter 922 and/or one or more of thesensors 910, 912, and 914 may be stored in a memory 924 and/or otherstorage device, or supplied directly to a processor 928, for exampleunder control of the processor 928 or controlled remotely from a remotecontrol and communication device (not shown). Alternatively, signalsfrom the A/D converter 922 and/or the sensors 910, 912, and 914 may becommunicated to a remote receiving device 930 via a transmitter/receiver934 for storage or analysis. Any suitable storage device 924 may be usedsuch as semiconductor memory, magnetic storage, optical storage, and thelike.

The memory can also be used to store various sensor and controlinformation including historical information and current informationacquired in real time.

In some examples, the control unit 900 may include a clock generator tosupply a digital clock signal to correlate signals from the sensors 910,912, and 914 to time. The A/D converter 922 and/or the sensors 910, 912,and 914 supply signals for storage or analysis at a suitable frequency.For many sensors, a suitable sample frequency may be in a range from 1to 100 Hertz, although lower or higher sample frequencies may be used. Asuitable sample frequency is defined to be sufficiently above a Nyquistsample rate of all signal frequencies of interest.

The processor 928 may be any suitable processing device such as acontroller, a microcontroller, a microprocessor, a central processingunit (CPU), a state machine, a digital logic, or any other similardevice. The processor 928 typically executes programs, processes,procedures, or routines that control various aspects of signalacquisition, analysis, storage, and communication. The processor 928 ispowered by a power source 906 that also supplies energy to othercomponents inside the housing 908 and to the sensors.

The filtered signal is input to the A/D converter 922 to convert thesignal to a form usable by the processor 928. Processor 928 performsoperations that convert the digital signal to one or more of severaluseful parameters indicative of the electromagnetic field. In oneexample, the processor 928 can sum the normalized values of the digitalsignals to generate an average or mean signal or determine changes inpolarity of the signal. The processor 928 can determine a plurality ofparameters, analyze the interrelationship of two or more parameters,detect variations of parameters over time, and the like.

The processor 928 acquires a plurality of electromagnetic field samplesfor a period of the electromagnetic field, and normalizes and sums thevalues to compute an average or mean value for the period.

Referring to FIG. 10, a schematic pictorial view shows an example of acontrol unit 900 that is configured to be attachable to a patient's armor leg for monitoring of extravasation, infiltration, phlebitis, andother conditions during infusion therapy. The control unit 900 performsoperations including measurement control, information processing, datastorage, and display of results. In some applications, the control unit900 may process data in real time or may collect data for subsequentanalysis.

In the illustrative example, the control unit 900 is housed in a case1010 a suitable size for attachment to a patient's arm or leg, taped toan alternative portion of the body, or mounted onto an IV pole. Thecontrol unit 900 has a visual display 1012 to facilitate viewing by thepatient, health care provider, or others. The visual display 1012, forexample a liquid crystal display, a computer screen, a personal digitalassistant (PDA) screen, a pager visual screen, cellular phone displayscreens, or any other suitable display. The display 1012 can displayvarious information including results and indications derived fromsensor information, alert notifications, current time and date as wellas time and date of pertinent events. The visual display 1012 can alsodisplay time and date of past and upcoming infusions. The control unit900 may have an alarm that generates a notification signal such as anaudio alarm, vibration, illumination signal, or other suitable types ofenunciator.

The control unit 900 stores and compares various types of information todiagnose tissue condition. One or more of various types of data can bestored, compared, and analyzed, for example including current data,reference data, baseline data, information trends, preset parameters,automatic comparison results, patient condition information for diseasecondition adjustments, environment information, cannula position andmotion information, and infusion flow information.

In some embodiments, the case 1010 may include an inlet fluid conductor1014 that is capable of connecting a proximal conduit 1016 to anintravenous fluid source 1018 such as a syringe, a pump, or an IV bag.An outlet fluid conductor 1020 connects a distal conduit 1022 to anintravenous discharge device 1024 that discharges fluid into a patient'sblood vessel.

Information stored in the control unit 900 may be visually presented onthe visual display 1012 and/or communicated to a remote receiving device930 via a transmitter/receiver 934 for storage or analysis. Thetransmitter/receiver 934 may be either a hardwire or wireless device.

Referring to FIG. 11, a flow chart depicts an example of a technique fordetecting a harmful tissue condition, for example intravascularinfiltration, intravascular extravasation or tissue necrosis, duringinfusion. In an initialization operation 1110 prior to infusioninitiation, a film barrier dressing with sensors is affixed to the skin1112 to one or more sites including the proposed vascular insertion siteof a needle or cannula into the vascular pathway. Interconnect lines areconnected from the film barrier dressing sensors to a control unit.Additional sensor dressing may be applied to other locations at risk forcomplications.

The sensors are capable of interrogating the tissue and receiving tissuecondition signals using one or more sensing technologies. Suitablesensing technologies may include bio-potential, bio-impedance,photonics, optical sensors, acoustic, ultrasound, and others. In oneexample, a photonics detector has an infrared generator and a photonicsdetector. The infrared generator produces a beam of light that scans thesurface skin and subcutaneous tissue during monitoring, causing thephotonics detector to generate a pulse signal that can be analyzed todetermine tissue condition.

The infusion system begins monitoring prior to insertion to obtainbaseline pre-infusion information 1114 at the plurality of sites in astart mode of operation. During the start mode, the control unit recordsthe baseline data and generates a normal characterization of tissue. Forexample, an extravasation analysis may begin by determining apre-injection baseline measurement of the tissue impedance by collectingpreliminary data prior to injection.

In an illustrative example, monitoring beings by injecting a currentacross the monitored tissue 1116, measuring a parameter 1118 such asimpedance during application of the current, and storing the parameter1120 in a memory. In one example, a constant sinusoidal alternatingcurrent is applied to the first electrode pair at a current ofapproximately 200 uA and frequency of about 20 kHz and the voltagepotential at the second electrode pair is measured. Other suitablecurrents and frequencies may be used. For example, Electrical ImpedanceTomography imaging typically uses frequencies above 1 kHz and less than100 kHz, although some applications may utilize frequencies up to 10 mHzand above. A system with capability to operate in a frequency rangebetween 10 kHz and 10 MHz is highly flexible.

An increase or decrease in electrical conductance and capacitance mayoccur resulting from changes in the tissue.

Continuous calculations of tissue impedance are made during theinjection therapy. The film barrier dressing remains affixed to thepatient during monitoring. Monitoring continues over time 1121 and themeasured and stored parameter is compared to past values 1122 includingthe stored baseline values. For multiple-site sensors, the infusionsystem compiles an impedance map 1124 that depicts impedancemeasurements over a two-dimensional or three-dimensional space.

A processor accesses the stored time and space impedance samples andperforms a thresholding and pattern recognition operation 1126. The filmbarrier dressing remains affixed to the patient and monitoring continuesover time during infusion. The infusion system determines the presenceor absence of infiltration and extravasation 1128 based on the thresholdanalysis and pattern recognition operation, and conveys results to adisplay screen 1130 for visual notification of a caretaker.

In an example of a thresholding and pattern recognition operation 1126,if data such as photonics, optical, and impedance are acquired, theanalysis may include operations of: (1) sensing infrared information andbio-impedance information, (2) comparing the information to presetthresholds, and (3) forming an information map indicative of thephysical or geometric contours of the acquired parameter. Various typesof information maps include photonics infrared reflection maps, opticalspectrographics maps, and bio-impedance maps.

In one example, extravasation is indicated if the impedance changes witha substantially consistent slope of ±0.5 Ω/s or more during infusion ata rate of at least 1000 cc over 24 hours or an intermittent infusion ofover 100 cc in one hour.

In an example, tissue impedance is considered to be affected byextravasation because ionic contrast media has lower impedance thantissue. For ionic contrast media extravasation, measured impedance isless than the measured tissue impedance prior to extravasation. Anon-ionic contrast media has higher impedance than tissue and causesincreased impedance during an extravasation.

The infusion system can send an alert signal 1132, such as an audioannunciation or alarm, when a harmful condition occurs. Accordingly, theinfusion system functions as a medical surveillance system to determinethe condition of tissue as a patient receives an infusion to allow acaretaker to intervene early, reducing complications associated withintravascular infusion. The alert notification may also includetransmission of the alert notification and analysis information in-theform of a status report that are sent to a remote device, for example bywireless transmission of patient status information, for example to acomputer, a pager, personal digital assistant (PDA), internet interface,or land line.

In another example, during the act of obtaining baseline pre-infusioninformation 1114, the baseline impedance represents the impedancemeasured at the zone of injection prior to starting injection. Thepattern recognition operation 1126 determines the occurrence ofextravasation by two characteristics, that the impedance varies from thebaseline by more than a first predetermined threshold and that the rateof change of impedance, called the slope, is consistently larger than asecond predetermined threshold.

To reduce false-positive indications of extravasation, a predeterminednumber of measurements are to deviate past the first predeterminedthreshold from the baseline, and the rate of change of the impedancemeasurements is to exceed a certain absolute value and do soconsistently.

In another example, the thresholding and pattern recognition operation1126 compiles individual historical and real time information on thestatus of a patient. Analyzed data includes continuously monitored datasamples from one or more cross-sectional tissue areas. The time historyof samples is analyzed to detect changes from reference information andbaseline values, and monitor data trends. The analysis may includeadjustments for known disease conditions, for example to predict likelytrends and determine results outside the prediction. Rapid value changesmay be indicative of physical movement or disruption of the needle orcatheter at the insertion site.

The infusion system 100 can alternatively be used to monitor forphysiological conditions relating to tissue grafting of artificial ornatural tissue to detect the presence of tissue necrosis that mayindicate rejection of new tissue.

In other applications the infusion system 100 can be used formonitoring, analysis, detection of complications, and generation ofcomplication alarms in hydration monitoring, wound closure,pharmacokinetic monitoring, monitoring and mapping of tissue in multipleablation freezing applications including radio frequency, laser, andcryosurgery applications, and others. For example, an infusion system100 that monitors overhydration and hypersensitivity to infusions andinfections may include temperature monitoring and heart electricalsignal monitoring that can detect circulatory overload. Infections cancause elevation in temperature and circulatory overload causes the heartrate to increase.

In another example, conductivity maps may be used to determine atemperature distribution. Temperature mapping can be used for manyapplications including object recognition in noninvasive surgery while asurgeon cuts or ablates tissue by cryotherapy, knife, laser, radiofrequency, or other cutting and ablating techniques. Mapping can be usedto visualize cancer and reduce cutting of healthy tissue. Temperaturemapping can be used for various applications including cancer treatmentin liver and other organ tissues, breast biopsy, and the like.Temperature mapping using sensors in the frame of a dressing with aninterior transparent window allows visualization in combination withtemperature mapping. Temperature mapping can also be used in combinationwith ultrasound imaging.

Following generation of the alarm, a caretaker typically visuallyexamines the site 1134 through the transparent dressing to detect IVcomplications such as dislodgement or movement of the catheter or needlefrom the original placement position. Complications are evidenced byvisible blood, fluid beneath the dressing, or movement of the cannula orneedle. Other visual cues of complication include tissue redness,swelling, tightness, and vein inflammation.

The caretaker can palpate the patient 1136 to detect tenderness orpatient discomfort, swelling, or increase in skin temperature. Swellingmay increase since IV infusions have an osmotic effect and draw waterinto the tissue.

The automatic alarm is a computer-aided diagnostic that enables thecaretaker to assess patient condition to determine whether to continueor terminate the IV infusion. The automatic alarm gives a capacity forearly detection of complications before symptoms are visible or beforequickly arising complications reach critical levels. Upon detection ofIV complications, the caretaker can terminate the infusion 1140.

Referring to FIG. 12, a schematic circuit diagram shows an impedancemodel of tissue that is useful for describing conductivityreconstruction in tissue. Techniques for determining and mappingconductivity distribution in tissue supply useful information ofanatomical and physiological status in various medical applications.Electrical Impedance Tomography (EIT) techniques are highly suitable foranalyzing conductivity distribution. Electrical characteristics oftissue include resistive elements and capacitive elements. EITtechniques involve passing a low frequency current through the body tomonitor various anatomical and physiological characteristics. The systemcan interrogate at multiple frequencies to map impedance. Analyticaltechniques involve forward and inverse solutions to boundary valueanalysis to tissue characteristics.

Multiple electrodes are placed in contact with tissue and a constantcurrent is applied to the tissue across a subset of the electrodes, andimpedance or resistance is measured at other electrodes. For example,tissue can be excited by an electric current and impedance is determinedby measuring the electric potential generated by the current. In otherexamples, a voltage can be generated and a current measured. Currentinterrogation and voltage measurement typically produces a more accurateimpedance measurement and has a lower output noise and bettersensitivity. Conductivity distribution can be mapped in two dimensionsor three dimensions. The illustrative technique solves the inverseproblem in full three dimensions. Two dimensional images are obtained byslicing the three dimensional images.

Referring to FIG. 13, a schematic block diagram shows an eight-electrodeconfiguration for a tissue impedance measurement. The multipleelectrodes can be connected to one impedance analysis circuit (notshown) via a multiplexer (not shown). Four electrodes 1310 are used toapply current to the tissue 1302, and four electrodes 1314 are used tosense body electrical activity that results from application of thecurrent. The differential voltage evoked by the applied current ismeasured at a differential amplifier 1320. In an illustrativeembodiment, the electrodes can be spaced equidistant about a circle,square, or any other suitable cross-section. The illustrative analysistechnique is highly flexible allows three-dimensional imaging when theelectrodes are formed in any configuration. In other embodiments, theelectrodes need not be equidistant. Any number of electrodes may beused. For example, a suitable sensor can use 32 or any other number ofelectrodes. Generally, the electrodes are spaced with a sufficient gapfor distinguishing electrical signals.

The illustrative imaging technique is very flexible and allowsinterrogation using any current pattern, using the complete electrodesmodel, rather than a point electrode model.

In one embodiment, the tomography method constructs a simple image with15 pixels. Other image configurations are suitable.

Referring to FIG. 14, an Electrical Impedance Tomography (EIT) blockdiagram shows a two-dimensional configuration of tissue at object Bmapped by a conductivity measurement device. A mathematical model of theforward problem for conductivity is depicted in equations (3–6) asfollows:∇·[δ′(P)·∇U′(P)]=0 at object B  (3)δ′(P)(∂U′(P)/∂η)=JPεS  (4)∫_(S) U′(P)ds=0  (5)

where U(P) is voltage and δ(P) is specific admittance of B, in which:δ′(P)=δ(P)′jωε(P)  (6)

S is surface boundary of B.

A boundary value problem is defined in which conductivity distribution σis real and positive throughout the field, ν is a potentialdistribution, η is an outward normal, J is applied flux, Ω is a domainof interest, and ∂Ω designates the domain boundry. The boundary valueproblem can be solved using a Finite Element Method (FEM) that producesa linear system of equations with the form shown in equation (7):Yν=c  (7)

where Y is a global stiffness matrix, ν is a vector representing thepotential distribution at node of the elements and c is effectiveapplied current at the nodes.

Referring to FIG. 15, a schematic pictorial diagram shows a FiniteElement Method (FEM) mesh. In the forward problem, the potentialdistribution of a domain is calculated given a known conductivitydistribution and a known current source for boundary conditions. In theinverse problem analysis, a voltage is measured and the currentinjection pattern is known. From the known voltage and current injectionpattern, the conductivity pattern is sought that produces the measuredvoltages. A difficulty is that in EIT, boundary potentials vary at anypoint in the conductivity distribution in a nonlinear manner.

The illustrative Electrical Impedance Tomography technique uses aregularized Newton-Raphson method to optimize the ill-posed inverseproblem for imaging and mapping. The optimization problem attempts tofind a best conductivity distribution that fits measured data. Imagereconstruction uses nr to optimize the ill-posed inverse problem forimaging and mapping. The optimization problem attempts to find a bestconductivity distribution that fits measured data. Image reconstructionuses Newton-Raphson regularization to stabilize the numerical solutionof the ill-posed inverse problem. Image reconstruction based on theNewton-Raphson method uses an efficient method for Jacobian matrixcomputation. Tikhonov regularization is used in the Newton-Raphsonmethod to stabilize image reconstruction.

The inverse problem in three dimensional Electrical Impedance Tomographyimaging is ill-posed and nonlinear. Several methods can be used forimage reconstruction of both low and high contrast conductivity. EITimaging can be cased on the Born approximation, particularly for lowcontrast conductivity reconstruction where little advantage is gained inrecalculation of the Jacobian.

Sensitivity Analysis using the Jacobian is depicted according to FIG.16. When a conductivity distribution changes from σ to σ+Δσ, thetransfer impedance change ΔZ for pairs of current and voltage electrodesA,B and C,D, respectively are shown in equation (8):ΔZ=−∫ _(Ω)Δσ(∇u(σ)/I _(u))·(∇ν(σ+Δσ)/I _(ν))dΩ  (8)

where u is the potential distribution over the field when the currentI_(u) is applied at electrodes A,B with a conductivity of σ. Similarly,ν is potential over the field when the current I_(ν) is applied atelectrodes C,D with a conductivity of σ+Δσ. Equation (8) assistssolution of the inverse problem by allowing estimation of a conductivityσ and calculation of u given current I_(u) in the forward analysis. Thedifference between the calculated potential distribution u and themeasured potential distribution ν gives value ΔZ. Using value ΔZ,conductivity distribution Δσ can be solved. The sensitivity method isvery general and allows determination of sensitivity directly and withany distribution of conductivity. Other less suitable methods only allowcalculation of sensitivity in a homogenous conductivity area.

A Newton-Raphson technique can be used to minimize a function φ withrespect to σ defined according to equation (9):φ=½(f−V)^(T)(f−V)  (9)

Minimization of φ is the Gauss-Newton iteration shown in equation (10):Δσ_(k) =−[f′(σ_(k))^(T) f′(σ_(k))]⁻¹ f′(σ_(k))^(T) [f(σ_(k))−V]  (10)

The φ iteration is ill-conditioned and further exacerbated by noisydata.

A simple iterative scheme can be used to combine the forward problem andthe inverse problem. First, estimate σ_(k) and consequently calculatedf. Second, compare the calculated f and the measured V. Third, adjustσ_(k) and calculate a new f. Fourth, iterate until ∥V−f∥ reaches aspecified criterion.

In a regularized Newton-Raphson method depicted in FIG. 17, an initialconductivity distribution is given 1710 which is presumed to be zero.The forward problem is solved 1712 and predicted voltages are comparedwith calculated voltages from the finite element model. Conductivity isupdated using a regularized inverse of the Jacobian. The process isrepeated 1714 until predicted voltages from the finite element methodagree with measured voltages. The update formula is shown in equation(11):σ_(n+1)=σ_(n)+(J _(n) *J _(n) +R)⁻¹ J _(n)*(V _(measured)−F(σ_(n)))  (11)

J_(n) is the Jacobian calculated 1716 with the conductivity σ_(n).V_(measured) is the vector of voltage measurements and the forwardsolution F(σ_(n)) is the predicted voltage from the finite element modelwith conductivity σ_(n). The matrix R is a regularization matrix thatpenalized extreme changes in conductivity, correcting instability in thereconstruction at the expense of producing artificially smooth images.To solve the full matrix inverse problem 1718, information obtained fromthe forward measurement is used. The inverse problem calculates aconductivity distribution σ_(n) given a set of current injectionpatterns I and a set of measured voltages V. The forward problem 1720calculates voltages f given a current injection pattern I and aconductivity distribution σ 1722.

While the invention has been described with reference to variousembodiments, it will be understood that these embodiments areillustrative and that the scope of the invention is not limited to them.Many variations, modifications, additions and improvements of theembodiments described are possible. For example, those skilled in theart will readily implement the steps necessary to provide the structuresand methods disclosed herein, and will understand that the processparameters, materials, and dimensions are given by way of example onlyand can be varied to achieve the desired structure as well asmodifications which are within the scope of the invention. Variationsand modifications of the embodiments disclosed herein may be made basedon the description set forth herein, without departing from the scopeand spirit of the invention as set forth in the following claims.

In the claims, unless otherwise indicated the article “a” is to refer to“one or more than one.”

1. A tissue monitoring apparatus comprising: a film barrier dressingcomprising a flexible membrane integrating one or more sensor elementsadapted to interrogate tissue at multiple electrical signal frequenciesand an adhesive layer adapted to couple the film barrier dressing to apatient's skin; a control unit adapted to couple to the one or moresensor elements in the film barrier dressing, the control unit adaptedto control the sensor elements to interrogate the tissue at selectedmultiple frequencies, sense one or more electrical signal parametersindicative of tissue condition in three-dimensional space, and execute acomplex number three-dimensional pattern recognition operation on theone or more sensed parameters to determine a subcutaneous mappingindicative of a tissue condition; a bio-impedance sensor including aplurality of sensor elements configured to acquire impedance signals inthree-dimensional space; and an electrical impedance tomographyprocessor executable in the control unit and adapted to execute anobject recognition operation on the impedance signals.
 2. A tissuemonitoring apparatus according to claim 1 wherein: the flexible membraneis at least partially transparent so that a patient's tissue underlyingthe film barrier dressing can be visually inspected.
 3. A tissuemonitoring apparatus according to claim 1 wherein: the film barrierdressing is a breathable barrier film that protects against infectionand functions as a structural member that is capable of securing anintravenous catheter.
 4. A tissue monitoring apparatus according toclaim 1 further comprising: a bio-impedance sensor, the control unitadapted to couple to the bio-impedance sensor and execute a patternrecognition operation in one or more dimensions on the impedance signalsto generate one or more sensor pathways using depth-selective sensing oftissue bio-impedance in a selected frequency range, generatecross-sectional surface measurements and subcutaneous measurements atone or more selected tissue depths by controlling the field extension ofthe sensor pathway, and determine the tissue condition.
 5. A tissuemonitoring apparatus according to claim 1 further comprising: abio-impedance sensor and an optical sensor, the control unit adapted tocouple to the bio-impedance sensor and to the optical sensor and adaptedto execute a pattern recognition operation in one or more dimensions onthe impedance signals and the optical signals to determine the tissuecondition.
 6. A tissue monitoring apparatus according to claim 1 furthercomprising: a bio-impedance sensor including a plurality of sensorelements configured to acquire impedance signals in three-dimensionalspace; and an electrical impedance tomography processor executable inthe control unit and adapted to execute a three-dimensional tomographyoperation on the impedance signals and generate one or more sensorpathways using depth-selective sensing of tissue bio-impedance in aselected frequency range, and generate cross-sectional surfacemeasurements and subcutaneous measurements at one or more selectedtissue depths by controlling the field extension of the sensor pathway.7. A tissue monitoring apparatus according to claim 1 furthercomprising: a bio-impedance sensor including a plurality of sensorelements configured to acquire impedance signals; and a fastreconstruction electrical impedance technique tomographic processorexecutable in the control unit and adapted to map the impedance signalssubcutaneously in three-dimensional space.
 8. A tissue monitoringapparatus according to claim 1 further comprising: an optical sensorcomprising a plurality of sensor elements configured to acquire opticalsignals in three-dimensional space, the sensor elements comprising aninfrared generator and a photonics detector; and a pattern recognitionprocessor executable in the control unit and adapted to sensethree-dimensional infrared and bio-impedance information in combination,compare the information to preset thresholds, and form an informationmap indicative of the physical or geometric contours of the infrared andbio-impedance information.
 9. A tissue monitoring apparatus according toclaim 1 further comprising: an optical sensor including a plurality ofsensor elements configured to acquire optical signals; and a patternrecognition processor executable in the control unit and adapted tosense infrared information and bio-impedance information in combination,compare the information to preset thresholds, and form an informationmap indicative of the physical or geometric contours of the acquiredparameter.
 10. A tissue monitoring apparatus according to claim 1further comprising: a biosensor adapted to perform analytic chemistrymeasurements of electrolyte levels for detecting electrolyteabnormalities.
 11. A tissue monitoring apparatus according to claim 1further comprising: a memory configured to store sensor informationincluding historical information and current information acquired inreal time; and an analysis process adapted to compare information in oneor more categories of a group including current data, reference data,baseline data, information trends, preset parameters, automaticcomparison results, patient condition information for disease conditionadjustments, environment information, cannula position and motioninformation, and infusion flow information.
 12. A tissue monitoringapparatus according to claim 1 further comprising: a sensor electrodearray including equally-spaced electrodes in a geometricalconfiguration; and a multiple-frequency analysis process executable inthe control unit that analyzes data from the multiple reference pointsto generate a spectrographic composite for monitoring over time.
 13. Atissue monitoring apparatus according to claim 1 further comprising: ananalysis process executable in the control unit that analyzes sensorinformation to detect one or more of infiltration, extravasation, bloodclots, and phlebitis in an intravascular infusion operation.
 14. Atissue monitoring apparatus according to claim 1 further comprising: ananalysis process executable in the control unit that analyzes sensorinformation to detect tissue necrosis and rejection in a tissue graft ofartificial or natural tissue.
 15. A tissue monitoring apparatusaccording to claim 1 further comprising: an analysis process executablein the control unit that analyzes sensor information to monitor tissuehydration.
 16. A tissue monitoring apparatus according to claim 1further comprising: an analysis process executable in the control unitthat analyzes sensor information to monitor wound closure.
 17. A tissuemonitoring apparatus according to claim 1 further comprising: ananalysis process executable in the control unit that analyzes sensorinformation for pharmacokinetic monitoring.
 18. A tissue monitoringapparatus according to claim 1 further comprising: an analysis processexecutable in the control unit that analyzes sensor information todetect tissue necrosis and rejection in a tissue graft of artificial ornatural tissue.
 19. A tissue monitoring apparatus according to claim 1further comprising: a transmitter in the control unit adapted to senddiagnostic information to a remote receiver for remote surveillance oftissue measurements and characteristics.
 20. A tissue monitoringapparatus according to claim 1 further comprising: a wirelesstransmitter in the control unit adapted to send diagnostic informationto one or more remote receivers for remote surveillance of tissuemeasurements and characteristics.
 21. A tissue monitoring apparatusaccording to claim 1 further comprising: a wireless transmitter in thecontrol unit adapted to send diagnostic information to one or moreremote receivers including one or more of personal computers, personaldigital assistants, pagers, remote visual display screens, and cellulartelephones.
 22. A tissue monitoring apparatus according to claim 1further comprising: a transmitter in the control unit adapted to sendcontrol information to an infusion pump controller for controllingintravascular infusion.
 23. A tissue monitoring apparatus according toclaim 1 further comprising: an analysis process executable in thecontrol unit that analyzes sensor information for monitoring and nappingtissue in multiple ablation freezing applications including radiofrequency, laser, and cryosurgery applications.
 24. A tissue monitoringapparatus comprising: means for flexibly covering and protecting apatient's skin; means integrated into the covering and protecting meansfor sensing one or more biological electrical signal parametersincluding a bio-impedance parameter sensed from a plurality of elementsand interrogating tissue at multiple electrical signal frequencies;means for acquiring three-dimensional biological electrical signalinformation including three-dimensional impedance signals from thesensing means using tissue interrogation at selected multiplefrequencies; means for analyzing patterns in the three-dimensionalbiological information using an electrical impedance tomographytechnique; and means for determining a patient tissue condition based onthe analyzed patterns.
 25. A tissue monitoring apparatus according toclaim 24 wherein: the covering and protecting means further comprises atransparent window enabling visualization of the patient's tissue andmeans for securing an intravenous catheter.
 26. A tissue monitoringapparatus according to claim 24 further comprising: means for measuringbio-impedance of the patient's tissue; means for interrogating thepatient's tissue using optical sensing; means for analyzing thepatient's tissue using pattern recognition of the bio-impedancemeasurements and optical sensing to determine the tissue condition; andmeans for forming an information map indicative of contours of theacquired measurements.
 27. A tissue monitoring apparatus according toclaim 24 further comprising: means for measuring bio-impedance of thepatient's tissue; and means for analyzing the patient's tissue usingpattern recognition of the bio-impedance measurements to determine thetissue condition.
 28. A tissue monitoring apparatus according to claim24 further comprising: means for measuring bio-impedance of thepatient's tissue; means for interrogating the patient's tissue usingoptical sensing concurrent with bio-impedance measurement; means forcomparing bio-impedance and optical information to preset thresholds;and means for forming an information map indicative of physical orgeometric contours of the optical and bio-impedance information.
 29. Atissue monitoring apparatus according to claim 24 further comprising:means for storing sensor information including historical informationand current information acquired in real time; and means for comparinginformation in one or more categories of a group including current data,reference data, baseline data, information trends, preset parameters,automatic comparison results, patient condition information for diseasecondition adjustments, environment information, cannula position andmotion information, and infusion flow information.
 30. A tissuemonitoring apparatus according to claim 24 further comprising: means foranalyzing sensor information to detect infiltration and extravasation inan intravascular (IV) infusion operation.
 31. A tissue monitoringapparatus according to claim 24 further comprising: means for analyzingsensor information to detect tissue necrosis and rejection in a tissuegraft of artificial or natural tissue.
 32. A tissue monitoring apparatusaccording to claim 24 further comprising: means for sending diagnosticinformation to a remote receiver for remote surveillance of tissuemeasurements and characteristics.
 33. A tissue monitoring apparatusaccording to claim 24 further comprising: means for sending diagnosticinformation to one or more remote receivers including one or more ofpersonal computers, personal digital assistants, pagers, remote visualdisplay screens, and cellular telephones for remote surveillance oftissue measurements and characteristics.
 34. A method of monitoring apatient tissue condition comprising: attaching a film barrier dressingto a patient skin surface, the film barrier dressing comprising aflexible membrane integrating one or more sensor elements and anadhesive layer capable of coupling to the patient's skin; acquiringinformation indicative of tissue condition via tissue interrogation atselected multiple electrical signal frequencies; communicatinginformation from the one or more sensor elements to a control unit;controlling the sensor elements to sense one or more parametersindicative of tissue condition in three-dimensional space; in a startmode, acquiring information from the one or more sensor elements andrecording baseline information; commencing an intravascular infusionoperation; in a test mode, acquiring information from the one or moresensor elements and recording test information; and comparing thebaseline information and the test information in three-dimensions usingelectrical impedance tomography using the one or more sensed parametersto determine a tissue condition.
 35. A method according to claim 34further comprising: storing sensor information including historicalinformation and current information acquired in real time; and comparinginformation in one or more categories of a group including current data,reference data, baseline data, information trends, preset parameters,automatic comparison results, patient condition information for diseasecondition adjustments, environment information, cannula position andmotion information, and infusion flow information.
 36. A methodaccording to claim 34 further comprising: sending diagnostic informationto a remote receiver for remote surveillance of tissue measurements andcharacteristics.
 37. A method according to claim 34 further comprising:sending diagnostic information to one or more remote receivers includingone or more of personal computers, personal digital assistants, pagers,remote visual display screens, and cellular telephones for remotesurveillance of tissue measurements and characteristics.